Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach

Abstract

The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present review looks to highlight the differences in genomic, proteomic, pathogenesis, and therapeutic strategies of SARS-CoV-2. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV-1 and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins was performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, makes available drugs ineffective.

Graphical abstract

Schematic representation of novel corona virus showing target proteins and its mechanism of host entry.

Highlights

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  The recent exposure to SARS-CoV-2 has affected entire world resulted >0.3 million deaths.

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  SARS-CoV-2, despite sharing 80% of genome similarity to SARS-CoV, its potential drug targets are highly conserved.

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  Despite high conservation among target proteins, structural differences make available drugs ineffective against SARS-CoV-2.

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  Cytokine storm is associated with viral inflammatory responses as seen in SARS-CoV-2 infection which may be targeted to handle COVID-19 patients.

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  Experimental trials of various FDA approved drugs are showing positive effects but further evaluation of large subject groups is required to confirm their efficacy.